The student management team: a vehicle for empowerment.
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Humans↗
Biomedical subjects
S Schenk
Publications and source records attributed to S Schenk.
NP teaches MDs about patient education.
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Education, Medical, Graduate↗
Multiple T cell specificities for Bet v I, the major birch pollen allergen, within single individuals. Studies using specific T cell clones and overlapping peptides.
Twenty-five T cell clones specific for Bet v I were established from the peripheral blood of two birch pollen-allergic patients. The T cell epitopes of these clones were mapped using dodecapeptides overlapping for 2 amino acids (neighbors share 10 residues) spanning the whole amino acid sequence of the protein (159 amino acids). In total, 7 epitopes could be detected. One donor displayed 6 distinct T cell specificities for the Bet v I molecule in 14 T cell clones; for the other donor, 4 stimulating peptides for 11 clones could be identified. Two T cell epitopes were recognized by both subjects. One of these might represent an immunodominant epitope located at amino acid position 77-92 of the Bet v I molecule, as in 13/25 T cell clones activation could be induced by this amino acid sequence. One T cell clone reacted with purified pollen-derived Bet v I, but neither with any peptide synthesized according to a Bet v I-encoding cDNA nor with the respective recombinant protein. Upon stimulation with allergen, the majority of the clones (21/24) revealed the TH0 or TH2 type of cytokine production (interleukin-4 production), indicating their importance in the pathogenesis of the allergic disease.
Allergens↗
Effects of serotonergic manipulations on cocaine self-administration in rats.
Rats were trained to self-administer cocaine (0.5 mg/kg/infusion) and were then pretreated with the 5-HT1A agonist 8-OH-DPAT (0.125, 0.25 or 0.5 mg/kg, SC). 8-OH-DPAT pretreatment produced a decrease in reinforced response rates. When the effect of 8-OH-DPAT (0.5 mg/kg, SC) on responding for a range of cocaine doses was assessed, the drug produced a decrease in response rates when lower doses of cocaine served as the reinforcer. Fluoxetine (10 mg/kg, IV), an indirect 5-HT agonist, also reduced reinforced response rates for a low dose infusion of cocaine. Rates of responding for infusions of higher cocaine doses were not affected by fluoxetine pretreatment during an FR1 schedule of reinforcement. When an FR10 schedule of reinforcement was imposed, reinforced response rates for infusions of higher doses of cocaine were also reduced. Thus, under conditions that produce high rates of responding (low dose infusion or high ratio requirements for an infusion) fluoxetine reduced responding. This effect may be due to the effects at the 5-HT1A receptor, since 8-OH-DPAT produced a similar effect on cocaine self-administration. Given that the effects of these 5-HT agonists are observed only when low doses of cocaine serve as the reinforcer or when task demands are high, it is possible that the suppression of responding reflects an effect that is not specific to the reinforcing impact of cocaine. An alternative explanation for these effects incorporates a concept of unit cost/cocaine infusion that allows for direct comparison across studies that employ different reinforcement schedules.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
Development and expression of sensitization to cocaine's reinforcing properties: role of NMDA receptors.
Acquisition of cocaine self-administration (0.125, 0.25 or 0.5 mg/kg/infusion) was assessed in rats that had received prior exposure to either saline or amphetamine (2.0 mg/kg). Acquisition of self-administration was dose-dependent, with the highest dose leading to the shortest latency to reliably discriminate between depression of a lever that resulted in drug delivery and an inactive lever. Latency to acquisition of the lever discrimination for rats that had received prior exposure to amphetamine was shorter than for the saline-pretreated counterparts in each cocaine dosage group. This suggests that repeated exposure to this drug prior to self-administration testing sensitized the rats to the reinforcing effects of cocaine. Co-administration of MK-801 (0.25 mg/kg, IP), a non-competitive NMDA antagonist, blocked the ability of chronic exposure to amphetamine to sensitize rats to cocaine. In experienced self-administering rats, acute pretreatment with MK-801 resulted in a loss of discriminative responding. The number of inactive lever responses was consistently higher than the number of active lever responses across all cocaine dosage groups. These data suggest that the NMDA receptor, possibly through interactions with dopamine systems, is critical for both the development and expression of sensitization to cocaine's reinforcing effects produced by intermittent preexposures to amphetamine.
Amphetamine↗
A comparison of the motor-activating effects of acute and chronic exposure to amphetamine and methylphenidate.
Acute exposure to methylphenidate (0.0, 5.0, 10.0, or 20.0 mg/kg) or amphetamine (0.0, 0.5, 1.0, 2.0, or 4.0 mg/kg) dose-dependently increased horizontal activity. The amphetamine-induced increase in activity was progressively augmented with repeated exposures over 7 days. In contrast, methylphenidate (20.0 mg/kg)-induced increases in activity became smaller with repeated exposures. Subthreshold doses of methylphenidate (1.0 or 5.0 mg/kg) were ineffective in stimulating motor activity even after 7 daily exposures. These findings suggest that, although sensitization develops with chronic amphetamine treatment, the consequence of chronic exposure to methylphenidate is tolerance. These data are discussed in terms of the different mechanisms through which methylphenidate and amphetamine affect central dopamine release.
Amphetamine↗
T cell clones specific for Bet v I, the major birch pollen allergen, crossreact with the major allergens of hazel, Cor a I, and alder, Aln g I.
Tree pollens are responsible for type I allergies during the flowering season in spring. Pollens from birch, hazel and alder constitute the most important allergen sources in this respect in the northern hemisphere. Human IgE antibodies, specific for the major allergens of these pollens, are known to crossreact, and in general every tree pollen allergic patient is sensitized to these three pollen allergens. In this study we investigated eight T-helper cell clones (CD3+, CD4+, TCR alpha/beta) with specificity for Bet v I, the major birch pollen allergen, as proved by reactivity with purified natural as well as with recombinant allergen. The T cell clones were used to investigate common T cell epitopes of the Bet v I molecule with Cor a I, the major allergen of hazel pollen and Aln g I, the major allergen of alder pollen. All eight T cell clones reacted with all three proteins with different intensity. Moreover, three T cell clones, which were known to react with immunodominant T cell epitopes on the Bet v I molecule, were tested for reactivity with dodecapeptides synthesized according to the corresponding homologous regions of the Cor a I and Aln g I sequence. All the peptides induced strong T cell proliferation, indicating the existence of multiple cross-reacting epitopes. These findings will have an impact on the production of vaccines for immunotherapy of tree pollen allergies.
Allergens↗
Improved method for electroporation of Staphylococcus aureus.
We have developed a significantly improved method for the electroporation of plasmid DNA into Staphylococcus aureus. The highest transformation efficiency achieved with this procedure was 4.0 x 10(8) transformants per microgram of plasmid pSK265 DNA. This represents a 530-fold improvement over the previously reported optimum efficiency of 7.5 x 10(5) transformants per microgram of plasmid DNA after electroporation of S. aureus cells [9]. Identical results were obtained when electrocompetent cells, which had been stored frozen at -80 degrees C, were used. The improved efficiency is due primarily to the use of a modified medium (designated as B2 medium) and secondarily to the use of 0.1-cm cuvettes. Several other plasmids (pI258, pMH109, and pSK270) were also electrotransformed into competent cells using our procedure, and for each plasmid, the transformation efficiency was significantly reduced compared to that observed when pSK265 DNA was used. With respect to plasmid pI258, the transformation efficiency was 3500-fold higher than that reported previously for transformation of this plasmid into S. aureus RN4220 [9]. The optimized electroporation procedure was less successful in transforming other staphylococci. Electrocompetent cells of S. aureus ATCC 29213 and S. epidermidis ATCC 12228 produced 5.5 x 10(5) and 5 x 10(3) transformants per microgram of pSK265 DNA, respectively.
Cell Membrane Permeability↗
Preexposure to amphetamine and nicotine predisposes rats to self-administer a low dose of cocaine.
The acquisition of low-dose (0.25 mg/kg/infusion) intravenous cocaine self-administration was measured in rats that had received nine daily injections of amphetamine (1.0 mg/kg, IP), nicotine (0.6 mg/kg base weight, SC) or vehicle. For control rats, the acquisition of self-administration was gradual with the number of responses per 2 h daily test session increasing between days 3 and 9. By comparison, rats preexposed with amphetamine and nicotine demonstrated elevated response means during the early days of testing, suggesting more rapid acquisition. All groups eventually reached similar asymptotic levels of responding. The enhanced responding observed during the early days of testing in the rats preexposed with amphetamine and nicotine was due to an increased number of subjects that reliably self-administered cocaine. Thus, the rats preexposed with amphetamine and nicotine seemed predisposed to the reinforcing effects of cocaine. In contrast to the self-administration data, preexposure to nicotine failed to sensitize rats to the locomotor activating effects of cocaine. In fact, the same preexposure regimen appeared to produce tolerance to this effect of cocaine. These data give evidence that different mechanisms may mediate sensitization to the reinforcing and locomotor activating effects of cocaine.
Amphetamine↗
Anticoagulation during pregnancy.
When anticoagulants are indicated during pregnancy, the needs of the mother as well as those of the fetus must be considered. Although anticoagulants may be indicated to prevent life threatening maternal thrombosis, oral anticoagulants such as warfarin have been associated with fetal anomalies. Patient education and early intervention with carefully monitored subcutaneous heparin can reduce both fetal and maternal risks.
Anticoagulants↗
Inherited hypercoagulable states: questions and controversies.
Inherited hypercoagulable states such as protein C, protein S, and antithrombin III deficiencies account for 15% to 20% of recurrent thromboembolic episodes. A common risk profile is associated with these disorders and guides the use of laboratory screening. The use of anticoagulants in inherited hypercoagulable states varies with a patient's personal and familial history of thrombosis. Special consideration is given to the need for anticoagulants perioperatively and during pregnancy.
Blood Coagulation Disorders↗
[Effects of various contraceptives on laboratory parameters in diagnosis of thyroid gland function with special reference to the free hormones FT4 and FT3].
The effect of different oral contraceptives with an estrogen content of 30-50 micrograms ethinyloestradiol on thyroid hormones and the binding protein TBG was investigated and quantified for 200 women. The sera of 220 normal persons were analysed to get normal values for T3, T4, FT4, Ft3, TBG and TSH. Under the influence of antiovulatory hormone treatment the thyroxin binding globulin increased to values above 32 mg/l in 65% of all euthyroid women. The median for T4 changed from 97 to 120 nmol/l, respectively from 2.3 to 2.8 nmol/l for T3. We think the combination of TSH, FT4 and T3 to be the best analytical tool for differential diagnosis of hyperthyreose. The FT4 level was nearly independent of variations in TBG concentration, so we can accept the normal range from 10-28 pmol/l for patients with contraceptives as well. In 16% of these euthyroid women the T3 level proved to be in the hyperthyroid range with values above 3.6 nmol/l. The FT3 determination is stronger influenced by protein changes caused by oestrogens than FT4 and should not be accepted as a favourite parameter for patients with oral contraceptives.
Adolescent↗
Isolation of chick tenascin variants and fragments. A C-terminal heparin-binding fragment produced by cleavage of the extra domain from the largest subunit splicing variant.
The extracellular-matrix glycoprotein, tenascin, consists of disulfide-linked subunits of 190, 200 and 230 kDa (the three splicing variants reported in chicken) and usually exists as a six-armed structure under the electron microscope. We used monoclonal antibodies to isolate and characterize different splicing variants and proteolytic fragments obtained from the native protein. Purified monomeric tenascin has a native molecular mass of 216 kDa and is structured as single arms. Tenascin fragments obtained by pepsin digestion bind to monoclonal antibody (mAb) TnM1 which is directed against epidermal-growth-factor-like repeats in the N-terminal half of all subunits. These fragments represent the thin proximal part of the tenascin arms and they are still partially linked to dimers and trimers via disulfide bridges. Using mAb Tn68, that reacts with a fibronectin-type-III repeat towards the C-terminus, a tenascin fragment, generated by treatment with pronase, can be isolated. Ultrastructurally, this fragment looks like the thicker distal part of the tenascin arms. Only the 230-kDa variant of tenascin gives rise to this distal fragment after cleavage within the alternatively spliced fibronectin-type-III repeats. Native tenascin and all fragments containing the distal part of its arms bind to heparin-agarose, whereas the proximal fragments do not. Oligomeric and monomeric tenascin inhibit fibronectin-mediated fibroblast spreading with comparable efficiency when added to the culture medium, while the proximal fragment has no effect. The distal fragment as well as reduced and alkylated tenascin are active in this assay, but only at higher molar concentrations when compared to the native protein.
Animals↗
Supersensitivity to the reinforcing effects of cocaine following 6-hydroxydopamine lesions to the medial prefrontal cortex in rats.
The effects of neurotoxic lesions to the medial prefrontal cortex on both the acquisition and maintenance of intravenous cocaine self-administration were examined. In one experiment, acquisition of intravenous cocaine self-administration (0.25, 0.5 or 1.0 mg/kg/infusion) was measured in separate groups of rats 14 days following either a sham or 6-hydroxydopamine lesion to the medial prefrontal cortex. For sham rats, the 1.0 and 0.5 mg/kg dose supported reliable self-administration as indicated by discriminative responding. These rats reliably chose a lever that resulted in the delivery of these doses of cocaine over an inactive lever. Reinforced response rates were reduced when 0.25 mg/kg was the available dose and there was a loss of discriminative responding for some of the rats suggesting that it was close to threshold for self-administration. For rats that sustained a 70% depletion of dopamine in the medial prefrontal cortex, the dose-response curve was an inverse function across the entire dose range tested. In contrast to the data from the control rats, lesioned rats had a high rate of reinforced responses and demonstrated good discrimination for all doses including 0.25 mg/kg/infusion, suggesting a supersensitive response to the initial reward effect of cocaine. Another group of rats was first screened for reliable cocaine self-administration (0.5 mg/kg/infusion) and then subjected to either the prefrontal cortical 6-hydroxydopamine or sham lesion. Dose-response curves for cocaine self-administration were compared 14 days following the infusions. The lesioned rats responded reliably for low doses of cocaine that were unable to maintain responding in sham rats. These data support the hypothesis that the medial prefrontal cortex plays an important role in cocaine self-administration.
Animals↗
Pre-exposure to amphetamine but not nicotine sensitizes rats to the motor activating effect of cocaine.
Rats were pretreated with nine daily injections of either d-amphetamine SO4(1.0 mg/kg, 1P), nicotine bitartrate (0.6 mg base/kg, SC) or saline. The motor activating effects of these drugs were measured for 60 min postinjection. On the tenth day, they were given a challenge injection of cocaine HCl (10 mg/kg) or saline and activity was again measured for 60 min postinjection. Both amphetamine and nicotine enhanced motor activity, although the stimulating effect of nicotine was not apparent until the third exposure to the drug. When the response to cocaine was assessed in these pre-exposed rats, only the amphetamine-treated animals were sensitized; they demonstrated a greater cocaine-induced motor activation than their saline-pretreated counterparts. The nicotine pre-exposed rats failed to demonstrate sensitization to the behavioral effect of cocaine; their response was not greater than the rats that had received pre-exposure to saline. These data demonstrate that the response to cocaine can be influenced by prior drug experience and that the influence may be dependent on the neurochemical specificity of the drug.
Amphetamine↗
GR38032F, a serotonin 5-HT3 antagonist, fails to alter cocaine self-administration in rats.
Recent data have supported a role for serotonin (5-HT) in the self-administration of cocaine by laboratory rats. More specifically, it has been suggested that 5-HT3 receptor antagonists may be useful in the treatment of drug abuse. To assess this possibility, we compared the effects of the 5-HT3 antagonist, GR38032F, with the dopamine D2 receptor blocker, haloperidol, on the intravenous self-administration of cocaine (0.5 mg/kg/infusion) in rats. The serotonin antagonist (0.01, 0.1 or 1.0 mg/kg, IP) failed to alter self-administration (0.5 mg/kg/infusion). In contrast, haloperidol (0.125 mg/kg, IP) increased responding for cocaine (0.5 mg/kg/infusion), and shifted the dose-response curve for cocaine self-administration to the right. These data fail to support a role for the serotonin 5-HT3 receptor system in the reinforcing properties of this psychostimulant. Rather, the 5-HT1 or 5-HT2 receptors may be the critical subtype.
Animals↗
Caffeine exposure sensitizes rats to the reinforcing effects of cocaine.
The present study examined the effect of pre-exposure to a moderate dose of caffeine (20 mg kg-1) on the acquisition of self-administration of cocaine (0.125 mg kg-1/infusion or 0.25 mg kg-1/infusion) in the rat. Rats pre-exposed to caffeine acquired self-administration more rapidly. Furthermore, sensitization to cocaine's reinforcing effects was accompanied by an increase in the neurochemical response of the mesolimbic dopamine system to an acute injection of cocaine (10 mg kg-1, i.p.) as measured by in vivo microdialysis. Thus, the data suggest that exposure to caffeine can increase the reinforcing effects of cocaine, possibly via an enhanced response to the mesolimbic dopamine system.
Animals↗
[Myocardial tomography with single photon emission computerized tomography (SPECT) technique in X syndrome].
Compared with the usual planar scintigraphy of the myocardium the single photon emission computer tomography (SPECT) has essential advantages. By means of the SPECT a three-dimensional reconstruction of the intersection image is possible which allows a judgement of the myocardium in the transversal, sagittal and coronary planes of section. The scans of the SPECT are richer in contrast and freer from overshadowings of normally of disturbedly perfused areas of the myocardium. 43 patients with angina pectoris complaints in angiographically normal coronary arteries (syndrome X) were examined by means of the SPECT under bicycle ergometer load and at rest. As radionuclide thallium-201 was used. 28 out of 43 patients (65%) showed disturbances of the perfusion, in which cases 21 patients with reversible ischaemias and 7 ones with cicatrised changes and an ischaemia of the marginal zone were conspicuous. Previous own investigations with the planar Tl-201 scintigraphy of the myocardium showed pathological findings in 66% of the cases with a syndrome X. The nearly identical results speak for the high reliability of the scintigraphy of the myocardium, but against the increase sensitivity of the SPECT in contrast to the planar scintigraphy of the myocardium.
Angina Pectoris↗